Medication adherence of individuals with a first episode of psychosis

OBJECTIVE: To determine rates of adherence to antipsychotic medication in first episode patients and the correlates of adherence in this group. METHOD: Subjects were the first 200 admissions to an Early Psychosis Program. Adherence was determined on a three-point scale. Symptoms, medication side-effects, quality of life, substance use and family involvement were examined longitudinally. RESULTS: In their first year in the program 39% were non-adherent, 20% inadequately adherent, and 41% adherent. Non-adherent patients demonstrated more positive symptoms, more relapses, more alcohol and cannabis use, reduced insight, and poorer quality of life. They were younger, had an earlier age of onset and less likely to have a family member involved in treatment. CONCLUSION: Results for this group are similar to those reported in the literature. Correlates are often the consequence of non-adherence. Non-compliance has to be anticipated and relationships maintained with patients and families to intervene as soon as possible to minimize the consequence of non-compliance.     

Gadolinium-DTPA enhanced gradient echo magnetic resonance scans in first episode of psychosis and chronic schizophrenic patients

Ten male schizophrenic patients underwent Gadolinium-DTPA (GdDTPA) enhanced magnetic resonance (MR) imaging to determine the utility of paramagnetic contrast agents in evaluating neuropathology. MR images enhanced by Gd-DTPA demonstrated no defect in the integrity of the blood-brain barrier.     

Proton magnetic resonance spectroscopy in multiple sclerosis

Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation.     

Proton magnetic resonance spectroscopy in Kennedy syndrome

OBJECTIVE: To seek regional metabolite abnormalities in patients with Kennedy disease (KD) using proton magnetic resonance spectroscopy. DESIGN: Nine patients with KD showing the typical phenotype without clinical signs of upper motor neuron involvement were compared with 17 male, age-matched, healthy control subjects. Relative metabolite concentrations for N-acetyl (NA) groups, choline-containing groups (Cho), phosphocreatine (Cr), and lactate (Lac) were determined in the brainstem and the motor region. RESULTS: Pathologic Lac signals suggesting impaired energy metabolism were absent in patients and controls. In the brainstem area, patients with KD showed a significant reduction in the NA/Cho metabolite ratio (P = .01). In the motor region, NA/Cho (P = .04) and NA/Cr (P = .03) ratios were significantly reduced. The reduction of the NA/Cho ratio in the motor region mainly resulted from decreased metabolite ratios in 3 patients. Changes in metabolite ratios did not correlate with the number of trinucleotide cytosine-adenine-guanine repeats from leukocytes. Because of the relatively small sample size due to the rarity of KD, these results should be considered preliminary. CONCLUSIONS: Spectroscopic data fail to provide further evidence for altered energy metabolism in KD. Metabolite changes in the brainstem indicate a reduction of the neuronal marker NA or elevated Cho. These findings may reflect neuronal loss or gliosis consistent with the known pathologic features. In a subset of patients, altered metabolite ratios best explained by neuronal loss suggest subclinical involvement of the motor region. The extent of metabolite changes does not correlate with the trinucleotide repeat length.     

Proton magnetic resonance spectroscopy in frontotemporal dementia

This study of frontotemporal dementia (FTD) was carried out to determine whether MR spectroscopy can provide an in vivo marker for the neuronal loss and gliosis that occur in this condition. We compared spectra in frontal and temporal regions known to be affected early in the course of the disease with spectra in the parietal lobe that is spared until late stages of FTD. We were interested in the relative concentrations of two compounds, NAA (a marker of neuronal integrity) and mI (a marker of gliosis), expressed as ratios to creatine (a relatively stable brain constituent). MR spectroscopy was performed on the temporal, parietal, and anterior cingulate cortices of five patients with the established semantic dementia form of FTD, two patients with the frontal form of FTD and 13 age matched controls. Structural MRI and neuropsychometry were also performed. Patients with FTD had reduced NAA/Cr in frontal and temporal, but not parietal lobes. The two patients with the frontal form of FTD had increased mI/Cr in their cingulate cortices. These data show for the first time that MR spectroscopy can reveal regionally selective abnormalities in patients with FTD. This opens up the possibility of using MR spectroscopy as a clinical tool to identify earlier presentations of the condition.     

Suicidality in first episode psychosis

Many studies have confirmed that the risk of suicide is high in the period after first presentation. There is relatively little information about the risk of suicide using illness onset as the starting point. We assessed suicidality in a cohort of 166 individuals from an urban catchment area during the period of untreated psychosis and at 4 year follow up. Nearly 10% of individuals attempted suicide prior to presentation. Four years later 18% had made a suicide attempt and 3% completed suicide. Suicide attempts prior to presentation were associated with a longer duration of untreated psychosis.     

Progressive membrane phospholipid changes in first episode schizophrenia with high field magnetic resonance spectroscopy

Patients with a first episode of schizophrenia generally have increased phospholipid membrane breakdown products within the brain, while findings in chronic patients have been inconsistent. In this study we examine progressive changes in phosphorus membrane metabolites in the same patient group through the early years of schizophrenia in brain regions associated with the disease. Sixteen never-treated and medicated first episode schizophrenic patients were assessed at 10 months and 52 months after diagnosis. Sixteen matched volunteers were assessed at baseline and after 35 months. Phospholipid membrane metabolism was assessed with phosphorous magnetic resonance spectroscopy in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex, parieto-occipital cortex, superior temporal gyrus and temporal pole. At 10 months, glycerophosphocholine was increased in the anterior cingulate in patients as compared to controls. Glycerophosphocholine was decreased in the anterior cingulate and increased in the posterior cingulate and left superior temporal gyrus; glycerophosphoethanolamine was decreased in the left thalamus and increased in the left hippocampus within patients over time. At 52 months, compared to controls phosphocholine was increased in the left thalamus and glycerophosphoethanolamine was increased in the left hippocampus. These results imply a gradual inclusion of brain regions in schizophrenia where an initial increase, followed by a decrease in phospholipid membrane metabolites was observed. This pattern, observed in the early years of schizophrenia, is consistent with excitotoxic neural membrane breakdown in these regions.     

Proton magnetic resonance spectroscopy in childhood brainstem lesions

Background Diagnosis of brainstem lesions in children based on magnetic resonance imaging alone is a challenging problem. Magnetic resonance spectroscopy (MRS) is a noninvasive technique for spatial characterization of biochemical markers in tissues and gives information regarding cell membrane proliferation, neuronal damage, and energy metabolism. Methods We measured the concentrations of biochemical markers in five children with brainstem lesions and evaluated their potential diagnostic significance. Images and spectra were acquired on a 1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g., choline), creatine, phosphocreatine, lactate, and lipids were measured within lesions located at the brainstem using Point-resolved spectroscopy sequences. Results Diagnosis based on localized proton spectroscopy included brainstem glioma, brainstem encephalitis, demyelination, dysmyelination secondary to neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In all but one patient, diagnosis was confirmed by biopsy or by clinical follow-up. Conclusions This small sample of patients suggests that MRS is important in the differential diagnosis between proliferative and nonproliferative lesions in patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have a rather misdiagnosis role.     

Duration of untreated psychosis vs. N-acetylaspartate and choline in first episode schizophrenia: a 1H magnetic resonance spectroscopy study at 4.0 Tesla

N-acetylaspartate (NAA) has been associated with neuronal integrity and function, and choline-containing compounds have been linked to neuronal membrane integrity. This study examined the influence of the duration of untreated psychosis, duration of prodromal symptoms and total length of untreated illness on these markers of neuronal loss or damage. In vivo 1H magnetic resonance spectroscopy data were acquired from 1.5-cc volumes in the left anterior cingulate and left thalamus of 19 never-treated first episode schizophrenic subjects using STEAM20 at 4.0 Tesla. Duration of untreated psychosis, prodrome and total length of untreated illness were correlated with levels of NAA and choline. No significant correlation was observed between NAA and duration of untreated psychosis and untreated illness in both regions examined. Thalamic NAA negatively correlated with duration of prodromal symptoms. A positive correlation between choline and duration of untreated psychosis was identified in both regions studied. Delays in treatment of psychotic symptoms of schizophrenia were not associated with a reduction in markers of neuronal integrity or function in contrast to longer prodromal periods, which were associated with lower NAA. Neuronal damage, potentially detectable via lower NAA, may be occurring before the onset of psychosis. Increased choline is associated with longer duration of untreated psychosis and could indicate that psychosis-related membrane alterations precede the appearance of NAA reductions observed by studies of chronic schizophrenia.     

Neurocognition and recovery in first episode psychosis

Cognitive functioning has been found to be a predictor of functional outcome of schizophrenia. It is unclear, however, whether clinical recovery can be predicted by scores on specific cognitive domains. The predictive value of specific neurocognitive domains and other clinical variables for symptomatic and functional outcome and clinical recovery after a 2-year follow-up is explored in a group of 51 patients with non-affective first-episode psychosis. A comprehensive neurocognitive battery was administered 18 and 41 weeks after inclusion. Other patient characteristics, which were expected to independently predict clinical recovery, were assessed at baseline. Several neurocognitive tests, especially tests measuring speed of processing, and among others, Duration of Untreated Psychosis (DUP), were significant predictors of clinical recovery. Poor neuropsychological performance accurately predicted non-recovery, but improved neuropsychological performance did not accurately predict recovery. This study confirms previous findings of an association between neurocognition and outcome, but the results also suggest that in order to accurately predict recovery, the role of other factors needs to be investigated.     

Stress and protective factors in individuals at ultra-high risk for psychosis, first episode psychosis and healthy controls

Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor in the onset and aggravation of psychotic symptoms, but such research in the early phases of psychosis is limited. Protective factors against the effects of stress might be the key to understanding some inconclusive findings and to the development of optimal psychosocial interventions. The present study compared self-reported levels of stress, self-esteem, social support and active coping in 32 patients with a first episode of psychosis (FEP), 30 individuals at ultra-high risk for psychosis (UHR) and 30 healthy controls. Associations with symptoms of psychosis were assessed in both patient groups. Individuals at UHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the UHR group reported lower social support and active coping than controls. These group differences could not be explained by age and dose of antipsychotic medication in the FEP group. In the UHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. Our findings show that individuals at UHR for psychosis experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes.     

Proton magnetic resonance spectroscopy of patients with parkinsonism

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson's disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ((1)H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. (1)H-MRS may be useful in monitoring patients with various types of parkinsonism.     

Proton magnetic resonance spectroscopy in brain white matter disorders

The advent of magnetic resonance imaging (MRI) has revolutionized the clinical approach to the evaluation of brain white matter disorders and has contributed significantly to expansion of the concept of these diseases. MRI is very sensitive at detecting white matter lesions, but conventional T1 and T2-weighted images do not provide specific pathological information about the lesions, and correlation between MRI lesion load and clinical disability is often weak. Proton magnetic resonance spectroscopy can provide chemical-pathological information of a given tissue invivo. The use of this MR technique in brain white matter disorders has shown to improve diagnostic classification and to provide surrogate measures useful for monitoring disease evolution and response to therapeutic intervention.The study was supported in part by grants from the Multiple Sclerosis Society of Canada and from the Progetto Sclerosi Multipla of the Istituto Superiore di Sanità, Rome, Italy.     

Proton magnetic resonance spectroscopy of brain metabolites in galactosemia

Brain edema may occur in infants with galactosemia and has been associated with accumulation of galactitol. Proton magnetic resonance spectra were obtained from 12 patients (four newly diagnosed neonates and eight patients on galactose-restricted diets, age range 1.7-47 years) and control subjects to measure brain galactitol levels in vivo and correlate them with urinary galactitol excretion. The results demonstrate that a markedly elevated brain galactitol level may be present only in newborn infants with galactosemia who exhibit massive urinary galactitol excretion.     

Proton magnetic resonance spectroscopy of the brain in dementia

Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progresson or effects of drug therapy.     

Frontolimbic glutamate alterations in first episode schizophrenia: evidence from a magnetic resonance spectroscopy study.

Glutamatergic dysfunction has been implicated in the pathophysiology of schizophrenia. In this study we performed absolute-quantification short-echo magnetic resonance spectroscopy (MRS) in nine patients with first episode schizophrenia and 32 group-matched control subjects to test the hypothesis of glutamatergic dysfunction at disease onset. Regions of interest were the left dorsolateral prefrontal cortex and the left hippocampus. In the patient group absolute concentrations of glutamate were significantly higher in the prefrontal cortex and near-significantly higher in the hippocampus. The glutamate signals significantly correlated with rating scores for schizophreniform symptoms. Absolute-quantification [1H]MRS can reveal glutamatergic abnormalities which might play an important role in the pathogenesis and course of schizophrenia.